Slow-binding inhibition of 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase
| Autor: | Casimir Blonski, Laurence Hecquet, Rémi Braga |
|---|---|
| Přispěvatelé: | Synthèse et étude de systèmes à intêret biologique (SEESIB), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2004 |
| Předmět: |
Time Factors
Stereochemistry Clinical Biochemistry Pharmaceutical Science Fructose-bisphosphate aldolase 01 natural sciences Biochemistry Enamine 03 medical and health sciences chemistry.chemical_compound Glyceraldehyde Drug Discovery Escherichia coli Pyruvates Molecular Biology Aldehyde-Lyases 030304 developmental biology Antibacterial agent 0303 health sciences Schiff base biology 010405 organic chemistry Spectrum Analysis Aldolase B Organic Chemistry Aldolase A Iminium 0104 chemical sciences Kinetics chemistry biology.protein Molecular Medicine |
| Zdroj: | Bioorganic and Medicinal Chemistry Bioorganic and Medicinal Chemistry, Elsevier, 2004, 12, pp.2965-2972. ⟨10.1016/j.bmc.2004.03.039⟩ Bioorganic and Medicinal Chemistry, 2004, 12, pp.2965-2972. ⟨10.1016/j.bmc.2004.03.039⟩ |
| ISSN: | 0968-0896 1464-3391 |
| DOI: | 10.1016/j.bmc.2004.03.039 |
| Popis: | 2-Keto-3-deoxy-6-phosphogluconate (KDPG) aldolase is a key enzyme in the Entner–Doudoroff pathway of bacteria. It catalyzes the reversible production of KDPG from pyruvate and d -glyceraldehyde 3-phosphate through a class I Schiff base mechanism. On the basis of aldolase mechanistic pathway, various pyruvate analogues bearing β-diketo structures were designed and synthesized as potential inhibitors. Their capacity to inhibit aldolase catalyzed reaction by forming stabilized iminium ion or conjugated enamine were investigated by enzymatic kinetics and UV–vis difference spectroscopy. Depending of the substituent R (methyl or aromatic ring), a competitive or a slow-binding inhibition takes place. These results were examined on the basis of the three-dimensional structure of the enzyme. |
| Databáze: | OpenAIRE |
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